We're back for Season 2, and Jon and James kick things off with one of their favourite topics: Incretin mimetics. The gut is the biggest endocrine organ in the body, and the data in steatotic liver disease is now as good as anything we have in Hepatology for steatotic liver disease.
James and Jon cover the basic pharmacology, how to start and titrate these drugs in practice, what to tell patients about stopping them, the muscle loss question, endoscopy and anaesthesia, and a brief look at where the evidence is going across cardiovascular disease, kidney disease, sleep apnoea, IBD, and cancer. There is a lot going on with these drugs and this episode is the primer.
As always comments, questions, feedback and suggestions please send to:
X: @2guystalkingit
Email: 2guystalkingit@gmail.com
Chapters
00:00 Intro: Season 2 is here
03:00 What are incretins? The gut as endocrine organ
06:30 Origin story: Gila Monster and the GLP-1 breakthrough 08:30 The drugs: semaglutide, tirzepatide, and what's coming 10:00 How they actually work: satiety, the brain, and fat oxidation
12:00 Who to start: patient selection and caution groups
13:30 Lean MASH and Southeast Asian BMI thresholds
16:00 Exercise, muscle loss, and the resistance training argument
18:30 Side effects: nausea, constipation, lipase, mood
21:00 Endoscopy and anaesthesia: what to do
24:00 Titrating in practice: James's approach
28:00 Stopping the drug: weight regain and the SURMOUNT data
33:00 Personalising treatment: who can stop, who shouldn't 35:00 Eating disorders, body image, and screening
37:00 MASH data: ESSENCE and Synergy-NASH trials
39:30 Oral formulations: what's available and caveats
40:30 Where bariatric surgery still fits
42:00 Broader indications: IBD, CVD, CKD, cancer
45:00 Global obesity trends and the public health message 47:00 Wrap-up
Papers discussed
ESSENCE trial
Synergy-NASH trial
SURMOUNT-MAINTAIN
Tirzepatide and fat oxidation, Cell Metabolism 2025
GLP-1 receptor agonists and 13 obesity-associated cancers
SELECT trial
FLOW trial
SURMOUNT-OSA
STEP 9: Semaglutide in obesity and knee osteoarthritis
Psoriatic Arthritis paper
